In order to be able to be inspired into the key target sites in the lungs of patients, inhalation drugs are typically provided in micronized form with average particle sizes of up to 10 microns. A number of devices have been developed for assisting the delivery of such medicaments into the lungs of patients. In one sort of device, a dry powdered inhaler (DPI) device, the medicament to be inhaled is dispensed into an air stream produced by the inspiratory action of the patient. A large number of such devices have been developed. The device may be a single dose device (e.g., wherein drug is dispensed from a pre-metered dosage means such as a capsule) or multidose (where the drug is stored in a reservoir and then metered prior to dispersal in the air stream or where the drug is pre-metered and then stored in multiple dosage packs such as blisters). In a number of DPI devices, the particulate drug is mixed with an excipient powder of larger average particle size and the drug particles are blended with the excipient to create a generally homogenous mixture. The larger particle size of the excipient results in the powder mixture being flowable, and the homogeneity of the mixture enable it to be metered into accurately measurable doses. This is of particular importance when only very small quantities of the drug are required in a dose. Excipient powders of this kind and pharmaceutical powder compositions for inhalation utilizing such excipients are described, for example, in U.S. Pat. No. 3,957,965.
The accurate metering of highly potent inhalant drugs causes particular problems, as the quantity of medicament in the composition relative to that of the carrier is likely to be particularly small (less than 1 part of drug to 50 parts of carrier). This is exemplified by the medicament formoterol, which is often administered to patients at a dose of less than 60 micrograms (doses may be as small as 6 micrograms).
U.S. Pat. No. 6,199,607 to Trofast describes a multi-step process for preparing a dry powder formoterol composition. The process as described includes the mixing of the components followed by micronization of the blend. The micronized particles were subsequently treated to remove amorphous areas in their crystal structure. The particles are then agglomerated, sieved, and spheronized, followed by a second sieving, spheronization and sieving.
What are needed then are simple methods for producing dry powder medicaments while maintaining desirable flow and deposition characteristics following dispersion.